Advances in the palliative treatment of patients with established metastatic malignancies have not only prolonged patient survival but also increased the incidence of bony metastases and subsequent pathological fractures. Thus, the prevention and effective treatment of fractures associated with metastatic defects in bone has become an increasingly important aspect of the care of cancer patients. Unfortunately, there are currently available only the crudest of clinical guidelines which may be used to assess the increased fracture risk associated with metastatic lesions in bond. Therefore, the appropriate time for prophylactic stabilization of impending fractures is not known. This investigation will be directed in the long term to the development of comprehensive biomechanical guidelines for the orthopaedic assessment and treatment of metastatic defects in long bones, the proximal femur, and the spine. A four-phase, staged approach will be used. In Task I we will conduct retrospective radiographic reviews of patients exhibiting metastatic lesions in those regions and determine the most frequent sites and approximate shapes of the lesions. As part of this task, we will also develop improved diagnostic imaging procedures for the description of lesion geometries. In Task II, we will determine in-vitro the strength reductions associated with simulated defects in long bones, the proximal femur and the spine. In Task III we will use finite element modeling of defects in these regions to provide a theoretical framework for interpreting the experimental results and assessing the sensitivity of the fracture risk predictors to individual patient variations. In Task IV we will combine these findings by developing structural predictors of fracture risk for individual patients with particular lesions. Biomechanical guidelines appropriate for each skeletal region will be developed and tested retrospectively in clinical populations. These guidelines should represent a significant improvement in the orthopaedic care of patients with metastatic defects in bone.